Aims/hypothesis We aimed to describe the shape of observed relationships between risk factor levels and clinically important outcomes in type 2 diabetes after adjusting for multiple confounders.Methods We used retrospective longitudinal data on 246,544 adults with type 2 diabetes from 600 practices in the Clinical Practice Research Datalink, 2006Datalink, -2012 Proportional hazards regression models quantified the risks of mortality and microvascular or macrovascular events associated with four modifiable biological variables (HbA 1c , systolic BP, diastolic BP and total cholesterol), while controlling for important patient and practice covariates. Results U-shaped relationships were observed between allcause mortality and levels of the four biometric risk factors. Lowest risks were associated with HbA 1c 7.25-7.75% (56-61 mmol/mol), total cholesterol 3.5-4.5 mmol/l, systolic BP 135-145 mmHg and diastolic BP 82.5-87.5 mmHg. Coronary and stroke mortality related to the four risk factors in a positive, curvilinear way, with the exception of systolic BP, which related to deaths in a U-shape. Macrovascular events showed a positive and curvilinear relationship with HbA 1c but a U-shaped relationship with total cholesterol and systolic BP. Microvascular events related to the four risk factors in a curvilinear way: positive for HbA 1c and systolic BP but negative for cholesterol and diastolic BP. Conclusions/interpretation We identified several relationships that support a call for major changes to clinical practice. Most importantly, our results support trial data indicating that normalisation of glucose and BP can lead to poorer outcomes. This makes a strong case for target ranges for these risk factors rather than target levels.Electronic supplementary material The online version of this article